The present invention relates primarily to a method for the therapeutic treatment of skin disorders, and more particularly to a topical application method, and compositions for use therein, for treating disorders of the skin which are caused by, or are dependent upon, depleted or inadequate collagen levels, and/or oxy- gen-containing free radicals, and/or oxidative generation of active metabolites via lipoxygenase pathways.
A wide variety of skin diseases and skin conditions in which the skin has undergone some form of damage or accelerated aging can be traced, either directly or indirectly, to processes which either deplete or inhibit synthesis of collagen, and/or generate oxygen-containing free radicals, and/or oxidatively generate biologically active metabolites, generally via lipoxygenase pathways, which in turn either directly act upon the skin or mediate other processes which have adverse effect on the skin. Such is the case, for example, in radiation-induced skin damage, particularly ultraviolet radiation-induced skin damage (e.g., sunburn), where it appears possible that the transfer of energy from the radiation to the skin results in the generation of excited oxygen species, such as singlet oxygen, the superoxide anion, and hydroxyl radicals, that can damage lipid-rich membranes with the subsequent activation of the chemical mediators of inflammation and/or damage the skin cell membrane and DNA, and also where it appears that the radiation releases arachadonic acid which is then oxidized via two predominant pathways to produce either prostaglandins or leukotrines. Such is also the case for skin damage resulting from chronic exposure to sunlight as well as in the natural aging process, where free radi- cal-induced damage appears to be involved and where collagen content is diminished. Such also is the case for disease conditions such as psoriasis, a chronic, recurrent, scaling skin disease of unknown etiology, where it is possible that hydroxyeicosatetraenoic acids and leukotrines generated by oxidation of arachidonic acid via the lipoxygenase pathway have a role in the pathogenesis of the disease.
An equally wide variety of therapeutic and/or prophylactic treatments have been suggested for preventing and/or alleviating skin conditions or diseases or collagen deficiencies. Critical to the success of any such methodology is the utilization of an active ingredient or ingredients which is effective for its purpose without concurrent generation of adverse side effects. Equally important, however, is the ability to employ an active ingredient which can be effectively delivered to the sites where it will act most efficaciously on the disease or condition (or afford protection therefrom). Generally speaking, it is thus necessary for the active ingredient to be deliverable in either an intact form or in a form whereby the active ingredient is exposed or released in the actual environment where its activity is needed. So too, it is of importance that the active ingredient be such as to be compatible with a base composition which facilitates topical application and which facilitates application in suitable dosages, and further that the active ingredient either be stable per se or have the ability to be stabilized in admixture with other components, so that preparations can be marketed with a suitably long shelf-life and such that prolonged activity can be obtained once topical application has been made.
In large part, known treatment and prevention methodologies for skin diseases and conditions fail in one or more of these criteria. Thus, known compounds which at least in theory might be useful in treating a skin disorder of the type described herein, either have potentially adverse side effects and/or cannot be delivered in active form and/or cannot be solubilized in base compositions and/or are unstable. See, e.g., Kaplan, D. L., e al., J. CuE. Aging & Cosmetic Derm. 1:115-121 (1988/89; this and all other references cited hereafter are hereby expressly incorporated herein by reference in their entireties). As such, the need very much exists for provision of a useful methodology for treatment and/or prevention of skin disorders in which collagen deficiency, and/or oxygen-containing free radicals, and/or biologically active products of oxidative processes are involved.